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| United States Patent |
6,110,506
|
|
Swinson
, et al.
|
August 29, 2000
|
DASC compositions, process for preparing same and suspensions containing
same
Abstract
The present invention provides DASC compositions, which upon introduction
into aqueous solutions, form stable, non-gritty suspensions. The present
invention also provides stable, non-gritty suspensions comprising the DASC
compositions of the present invention admixed in aqueous solutions. In
addition, the present invention provides processes for preparing the
suspensions which comprise admixing the DASC compositions of the present
invention with aqueous solutions. Finally, the present invention provides
processes for preparing the DASC compositions of the present invention.
| Inventors:
|
Swinson; Joel (Ooltewah, TN);
Giles; Richard D. (Signal Mountain, TN);
Pitkin; Jack (Chattanooga, TN);
Fleming; Glenda (Chattanooga, TN);
Blum; David B. (Wayne, NJ)
|
| Assignee:
|
Chattem Chemicals, Inc. (Chattanooga, TN)
|
| Appl. No.:
|
475620 |
| Filed:
|
December 30, 1999 |
| Current U.S. Class: |
424/686; 424/489; 424/490; 424/715; 514/819; 514/820; 514/925; 514/926; 514/927; 514/928; 514/937; 514/951; 514/952 |
| Intern'l Class: |
A61K 009/10; A61K 033/10; C01B 031/30; A01N 059/06; A01N 025/04 |
| Field of Search: |
424/686,489,490,715
514/819,820,925,926,927,928,937,951,952
556/175,182,183,184,185
423/420.2
|
References Cited
U.S. Patent Documents
| 2783179 | Feb., 1957 | Grote | 424/686.
|
| 2999790 | Sep., 1961 | Alford | 424/689.
|
| 3272704 | Sep., 1966 | Beekman | 424/683.
|
| 3591680 | Jul., 1971 | Greene et al. | 424/601.
|
| 3629229 | Dec., 1971 | Schmank | 536/121.
|
| 3911090 | Oct., 1975 | Hem et al. | 423/419.
|
| 4112072 | Sep., 1978 | Rubino et al. | 424/683.
|
| 4115553 | Sep., 1978 | Rubino et al. | 424/683.
|
| 4676984 | Jun., 1987 | Wu et al. | 424/689.
|
| 5874112 | Feb., 1999 | McNally et al. | 424/690.
|
| 5914135 | Jun., 1999 | Dubek et al. | 424/687.
|
| Foreign Patent Documents |
| 275834 | Jul., 1988 | EP.
| |
Other References
Shad, D.N. et al., "Mechanism of interaction between polyols and aluminum
hydroxide gel," Journal of Pharmaceutical Sciences, vol. 70(10), pp.
1101-1104, Oct. 1981.
|
Primary Examiner: Pak; John
Attorney, Agent or Firm: Amster, Rothstein & Ebenstein
Parent Case Text
This is a continuation of application Ser. No. 08/824,509, filed Mar. 26,
1997, the contents of which is hereby incorporated by reference in its
entirety.
Claims
What is claimed:
1. A process for preparing a dihydroxy aluminum sodium carbonate
(DASC)/polyol powder comprising the steps of: (i) synthesizing DASC; (ii)
isolating the synthesized DASC to provide isolated, undried DASC; (iii)
mixing the isolated, undried DASC with water and at least one polyol
selected from the group consisting of sorbitol, glycerin, mannitol,
maltodextrin and fructose to form an aqueous DASC/polyol suspension; and
(iv) drying the aqueous DASC/polyol suspension to form a DASC/polyol
powder.
2. The process of claim 1, wherein DASC is synthesized by reacting an
organoaluminum compound with a carbonate in an aqueous solution.
3. The process of claim 2, wherein the molar ratio of organoaluminum
compound:carbonate is 1:1 to 1:3.
4. The process of claim 2, wherein the organoaluminum compound and the
carbonate are reacted at a temperature of -20.degree. C. to 120.degree. C.
5. The process of claim 2, wherein the organoaluminum compound and the
carbonate are reacted at room temperature.
6. The process of claim 2, wherein the organoaluminum compound is an
aluminum alkoxide.
7. The process of claim 6, wherein the aluminum alkoxide is aluminum
iso-propoxide, aluminum ethoxide or aluminum sec-butoxide.
8. The process of claim 7, wherein the aluminum alkoxide is aluminum
iso-propoxide.
9. The process of claim 2, wherein the carbonate is sodium bicarbonate or
sodium carbonate.
10. The process of claim 9, wherein the carbonate is sodium bicarbonate.
11. The process of claim 2, wherein the organoaluminum compound is aluminum
iso-propoxide and the carbonate is sodium bicarbonate.
12. The process of claim 1, wherein the synthesized DASC is isolated by
filtration, centrifugation, settling, decanting or a combination thereof.
13. The process of claim 1, wherein the isolated, undried DASC is washed
with water before being mixed with the aqueous polyol.
14. The process of claim 1, wherein the weight ratio of DASC:polyol in step
(iii) is 0.67:1 to 19:1.
15. The process of claim 1, wherein the weight ratio of DASC:polyol in step
(iii) is 1.5:1 to 5:1.
16. The process of claim 1, wherein the polyol is sorbitol.
17. The process of claim 1, wherein the aqueous DASC/polyol suspension is
dried by air-drying, oven-drying, fan-drying, spray-drying, or a
combination thereof.
Description
FIELD OF THE INVENTION
The present invention is directed to improved dihydroxy aluminum sodium
carbonate (DASC) compositions, which unlike prior art DASC, form stable,
non-gritty suspensions in aqueous solutions. The improved properties of
the DASC compositions of the present invention render the compositions
particularly useful as components of liquid antacids, and other consumer
and industrial products, for which stable, non-gritty suspensions are
desirable.
BACKGROUND OF THE INVENTION
DASC is a known aluminum salt which exhibits excellent acid neutralizing
capacity, and therefore is particularly useful in antacid formulations.
(See, Grote, U.S. Pat. No. 2,783,179, issued Feb. 26, 1957). However, the
use of prior art DASC as the active ingredient in antacid formulations has
been generally limited to non-liquid formulations (e.g. Rolaid tablets)
because prior art DASC does not form stable aqueous suspensions at
concentrations that produce acceptable acid neutralizing capacity. In
addition, even dilute suspensions of prior art DASC possess an undesirable
gritty appearance and taste, and rapidly form a sediment layer.
Several attempts have been made to stabilize aluminum hydroxide
suspensions. For example, Alford, U.S. Pat. No. 2,999,790, issued Sep. 12,
1961, described combining hexitols such as sorbitol and mannitol with
aluminum hydroxide gels in water to prevent thickening and hardening of
the aluminum hydroxide gels.
Greene, et al., U.S. Pat. No. 3,591,680, issued Jul. 6, 1971, described the
use of hydroxypropyl cellulose for stabilizing antacids such as magnesium
carbonate, magnesium hydroxide, aluminum hydroxide, or calcium carbonate,
which essentially involved slurrying the dry actives with water and
hydroxypropyl cellulose.
Schmank, U.S. Pat. No. 3,629,229, issued Dec. 21, 1971, described water
soluble antacid formulations that were prepared by reacting aluminum
powder or aluminum isopropoxide with polyhydroxyl hydrocarbons.
Rubino, et al., U.S. Pat. No. 4,112,072, issued Sep. 5, 1978, described
antacid compositions that were prepared by codrying hydrous, gelatinous
aluminum-hydroxide materials with di- or trihydroxy alcohols.
Beekman, U.S. Pat. No. 3,272,704, issued Sep. 13, 1966, described antacid
compositions that were prepared by co-drying aluminum hydroxide and
magnesium hydroxide gels with hexitols.
Hem, et al., U.S. Pat. No. 3,911,090, issued Oct. 7, 1995, described
antacid compositions containing silicate anions and aluminum hydroxy
carbonates which purportedly possess the antacid properties of liquid
aluminum hydroxide gels.
However, prior to the present invention, no methods have been taught or
suggested for preparing DASC compositions which, upon introduction into
aqueous solutions, results in suspensions that have the desired properties
of stability and non-grittiness.
SUMMARY OF THE INVENTION
The present invention is based upon the discovery by the inventors of DASC
compositions, which unlike prior art DASC, form stable, non-gritty
suspensions in aqueous solutions. The DASC compositions of the present
invention, unlike prior art DASC, also can be formulated so that upon
introduction into aqueous solutions, the resulting suspensions not only
possess the aforementioned desired physical properties, but also have
acceptable acid neutralizing capacities. Accordingly, the DASC
compositions of the present invention are particularly desirable for use
in liquid antacid formulations.
In addition to stability and non-grittiness, the DASC compositions of the
present invention also can be formulated to have gelling and/or
translucent properties. Accordingly, the DASC compositions of the present
invention are also suitable for use as components of other consumer or
industrial products such as tooth pastes, soaps, detergents,
pharmaceuticals, lotions, nutriceuticals, plastic additives, chemical
foaming agents, acid scavengers, gellants, cleaners, and the like, for
which stable and non-gritty, and/or gelling and/or translucent properties
are desirable.
The properties of the DASC compositions of the present invention relate to
the manner in which the compositions are prepared. Specifically, it has
been found that if DASC is synthesized under certain temperature
conditions, then the resulting dried DASC composition, when reconstituted
in an aqueous solution, results in a suspension having the desired
properties. It also has been found that if at least one polyol is included
in freshly synthesized DASC before drying, or is included during the
reaction of DASC, then the resulting co-dried DASC/polyol composition,
when reconstituted in an aqueous solution, will also result in a
suspension that possesses the desired properties of stability and
non-grittiness. In addition, depending upon the choice of polyol, the
suspensions also may be prepared to be translucent and/or gelling.
Accordingly, in addition to the improved DASC compositions and suspensions
containing the same, the present invention also provides processes for
preparing the DASC compositions of the present invention.
Additional objects of the invention will be apparent from the description
which follows.
DETAILED DESCRIPTION OF THE INVENTION
The composition of the present invention is directed to a powder that
comprises DASC, which upon introduction into an aqueous solution, forms a
stable, non-gritty suspension. As used herein, "stable" means that the
powder does not settle or separate in the suspension but rather stays in
solution resulting in a suspension having a homogeneous appearance. This
stability lasts for at least three months, preferably at least six months,
and most preferably for up to a year or more. "Non-gritty" means that the
suspension has only minor or no grittiness.
The powder of the present invention also can include at least one polyol.
Suitable polyols include but are not limited to sorbitol, glycerin,
mannitol, maltodextrin, pentaerythritol, fructose, glucose and sucralose.
However, as discussed in the Examples below, the inventors of the present
invention have found that polyols such as propylene glycol, 1,3-butylene
glycol, neopentyl glycol, polyethylene glycol and sodium
carboxymethylcellulose do not result in suspensions having the desired
stability and non-gritty properties. Accordingly, such polyols are not
included within the term "polyols" as used herein. The ratio of
DASC:polyol to arrive at the desired properties may vary. However, in the
preferred embodiment, the weight ratio of DASC:polyol is 0.67:1 to 19:1
(40-95% DASC), and more preferably is 1.5:1 to 5:1 (60-83% DASC).
The DASC powder of the present invention is prepared by reacting an
organoaluminum compound with a carbonate in an aqueous solution at a
temperature of between about -20.degree. C. and about 10.degree. C. The
molar ratio of organoaluminum compound:carbonate is preferably 1:1 to 1:3.
Sodium chloride or isopropyl alcohol also may be added to the reaction
mixture. Suitable organoaluminum compounds include aluminum alkoxides such
as aluminum iso-propoxide, aluminum ethoxide and aluminum sec-butoxide.
Preferably, the organoaluminum compound is aluminum iso-propoxide. The
inventors of the present invention have found that the use of aluminum
chloride or sodium aluminate does not result in a suspension having the
desired properties. Accordingly, aluminum chloride and sodium aluminate
are not included within the term "organoaluminum compound" as used herein.
The carbonate includes but is not limited to sodium bicarbonate and sodium
carbonate, but is preferably sodium bicarbonate.
After the DASC is prepared using the above process, it is isolated by
methods known in the art such as filtration, centrifugation, settling,
decanting or a combination thereof. For batch preparations, filtration is
preferred. The DASC may then be washed with water following isolation to
remove isopropyl alcohol formed during the reaction. The isolated DASC is
then dried into powder form by suitable methods including but not limited
to air-drying, oven-drying, fan-drying, spray-drying or a combination
thereof.
When at least one polyol is included in the powder with DASC, it has been
found that the desired DASC/polyol powder can be prepared by certain
modifications to the above process. Specifically, the polyol(s) can be
added directly to the freshly prepared wet DASC before or after the
isolation step, or can be combined with the organoaluminum compound and
the carbonate reactants before DASC is formed. However, it is preferred
that the polyol is added after DASC has been isolated since it has been
found that when the polyol is combined with DASC or the reactants before
isolation of DASC, some of the polyol may be lost in the isolation step.
The inventors also have found that dry DASC cannot be combined with the
polyol in water and result in an aqueous DASC/polyol suspension having the
desired properties. Accordingly, the use of previously prepared dry DASC
is not encompassed by the processes of the present invention.
The organoaluminum compound and carbonate used in preparing the DASC/polyol
powder are the same as described above for the DASC powder, with aluminum
iso-propoxide and sodium bicarbonate being the preferred reactants.
However, the reaction can be performed at a broader temperature of between
about -20.degree. C. and about 120.degree. C. For the sake of ease, the
reaction is preferably performed at room temperature. Suitable polyols
again include but are not limited to sorbitol, glycerin, mannitol,
maltodextrin, pentaerythritol, fructose, glucose and sucralose. However,
hexitols such as sorbitol and mannitol are preferred.
The present invention also provides a stable, non-gritty suspension
comprising either the DASC powder or the DASC/polyol powder of the present
invention. The suspension may be prepared by admixing the powder with an
aqueous solution at a w/w that results in the suspension having the
desired physical properties. The inventors of the present invention have
found that at a w/w of 1-15%, preferably at a w/w of 1-10%, and most
preferably at a w/w of 2-6%, the suspension will be stable and non-gritty.
However, it is within the confines of the present invention that higher or
lower concentrations of the powder may be utilized if they result in a
suspension having the desired properties.
The present inventors also have found that the suspensions of the present
invention, depending upon the choice and concentration of polyol in the
DASC/polyol powder, also possess other desirable properties in addition to
stability and non-grittiness. For example, it has been found that the use
of sorbitol, glycerin, mannitol, maltodextrin, pentaerythritol and
fructose as the polyol can result in a suspension that not only is stable
and non-gritty, but also is translucent. As used herein, "translucent"
means that the suspension is not opaque such that light can pass through
the suspension in a manner that permits the outline of objects (although
not the details of such objects) to be seen through the suspension. In
addition, it has been found that the use of polyols such as mannitol or
fructose, for example, can result in a suspension that also has gelling
properties.
Based upon the aforementioned properties, the powders or suspensions of the
present invention are useful as components of various consumer or
industrial products for which such properties are desirable. Such products
include but are not limited to liquid antacids, tooth pastes, soaps,
detergents, pharmaceuticals, lotions, nutriceuticals, plastic additives,
chemical foaming agents, acid scavengers, gellants, cleaners, and the
like. The formulation of such products with the powders and suspensions of
the present invention are well within the purview of those skilled in the
art.
However, because the suspensions are stable and non-gritty, and can be
formulated to have an acceptable acid neutralizing capacity, the
suspensions of the present invention are preferably used as the active
ingredient in liquid antacid formulations. In this connection, it is
preferred that the suspensions of the present invention have an acid
neutralizing capacity (ANC) of 0.1-3.0, and more preferably an ANC of
0.5-1.0. However, higher or lower ANC values can be obtained if desired.
The ANC can be determined using the procedures outlined in the U.S.
Pharmacopoeia. In addition to the stability and non-gritty properties, the
antacids can also be formulated to have gelling and/or translucent
properties, as described above. In the particularly preferred embodiment,
the liquid antacids are translucent, stable, non-gritty and non-gelling.
Liquid antacids having these properties can be prepared as described in
the examples below using polyols such as such sorbitol, glycerin,
mannitol, maltodextrin, pentaerythritol and fructose. Finally, it is
within the confines of the present invention that the liquid antacid
formulations may be combined with flavoring agents, coloring agents,
preservatives, and the like, if so desired.
The present invention is described in the following examples which are set
forth to aid in the understanding of the invention, and should not be
construed to limit in any way the invention as defined in the claims which
follow thereafter.
EXAMPLE 1
Dry DASC And Water
A 5% (w/w) aqueous suspension of dry DASC, previously prepared essentially
as described in Example 1 of U.S. Pat. No. 2,783,179, was stirred for
about 30 minutes with gentle heating in order to ensure complete
dispersion. The results are summarized in Table 1, and are as follows:
ANC, not determined; Appearance, opaque; Stability, bad settling;
Grittiness, bad; Evaluation, unacceptable.
EXAMPLE 2
DASC(Cold) Only/Salt Solution
97.9 g of sodium bicarbonate were added to 440 g of salt solution
containing 40 g of sodium chloride and 400 g of ice, and cooled to
-13.degree. C. 204 g (1 mole) of aluminum iso-propoxide were then added to
the mixture and stirred for 1 hour. The resulting precipitate was isolated
by vacuum filtration, air dried, and then oven dried at 100.degree. C.
overnight. A 5% (w/w) aqueous suspension of the material was then
prepared, and stirred for about 30 minutes with gentle heating in order to
ensure complete dispersion. The results are summarized in Table 1, and are
as follows: ANC, 1.265; Appearance, semi-opaque; Stability, excellent;
Grittiness, none; Evaluation, acceptable.
EXAMPLE 3
DASC(Cold) Only
146.9 g (1.75 moles) of sodium bicarbonate and 60 g isopropyl alcohol were
added to 540 g of ice water, and cooled to -10.degree. C. with dry ice.
306 g (1.5 moles) of aluminum iso-propoxide were then added to the
mixture. The resulting precipitate was isolated by vacuum filtration, air
dried, and then oven dried overnight. A 5% (w/w) aqueous suspension of the
material was then prepared, and stirred for about 30 minutes with gentle
heating in order to ensure complete dispersion. The results are summarized
in Table 1, and are as follows: ANC, 1.065; Appearance, semi-opaque;
Stability, excellent; Grittiness, none; Evaluation, acceptable.
EXAMPLE 4
Dry DASC(Room Temp.) And Sorbitol
Dry DASC, previously prepared essentially as described in Example 1 of U.S.
Pat. No. 2,783,179, was reslurried with enough sorbitol to give a
sorbitol/Al.sub.2 O.sub.3 ratio of approximately 1:1. The slurry was air
dried, and then oven dried at 100.degree. C. overnight. A 5% (w/w) aqueous
suspension of the material then was prepared, and stirred for about 30
minutes with gentle heating in order to ensure complete dispersion. The
results are summarized in Table 1, and are as follows: ANC, 0.920;
Appearance, opaque; Stability, bad settling; Grittiness, bad; Evaluation,
unacceptable.
EXAMPLE 5
DASC(Hot); Sorbitol Before Filtration
147 g (1.75 moles) of sodium bicarbonate were added to 540 g of water. 306
g (1.5 moles) of aluminum isopropoxide, heated to 100.degree. C., then
were added to the mixture and stirred for 1 hour. 128 g of a 70% sorbitol
solution (90 g of 100% sorbitol and 38 g of water) then were added to the
mixture, and stirred for 1 hour. The resulting precipitate was isolated by
vacuum filtration, air dried, and then oven dried at 100.degree. C.
overnight. More than 50% of the sorbitol was lost in the filtration
process. A 5% (w/w) aqueous suspension of the material then was prepared,
and stirred for about 30 minutes with gentle heating in order to ensure
complete dispersion. The results are summarized in Table 1, and are as
follows: ANC, 0.947; Appearance, translucent; Stability, excellent;
Grittiness, none; Evaluation, preferred.
EXAMPLE 6
Sodium Bicarbonate/Sorbitol/AIP(Hot)
147 g (1.75 moles) of sodium bicarbonate, 540 g of water, and 390 g of a
70% sorbitol solution (i.e. 273 g of 100% sorbitol and 170 g of water)
were mixed. 306 g (1.5 moles) of aluminum iso-propoxide, heated to
100.degree. C., then were added to the mixture and stirred for 2 hours.
The resulting precipitate was isolated by vacuum filtration. Roughly half
the batch filtered rather well. The filtered liquid and unfiltered solid
were recombined to prevent loss of sorbitol, air dried, and then oven
dried at 100.degree. C. overnight. A 5% (w/w) aqueous suspension of the
material then was prepared, and stirred for about 30 minutes with gentle
heating in order to ensure complete dispersion. The results are summarized
in Table 1, and are as follows: ANC, 0.677; Appearance, translucent;
Stability, excellent; Grittiness, none; Evaluation, acceptable.
EXAMPLE 7
DASC(Cold); 70% Sorbitol After Filtration
146.9 g (1.75 moles) of sodium bicarbonate and 60 g isopropyl alcohol were
added to 540 g of ice water, and cooled to -10.degree. C. with dry ice.
306 g (1.5 moles) of aluminum iso-propoxide then were added to the mixture
and stirred. The resulting precipitate was isolated by vacuum filtration
and reslurried with 128 g of a 70% sorbitol solution (i.e. 90 g of 100%
sorbitol and 38 g of water). After mixing, the resulting mixture was air
dried, and then oven dried at 100.degree. C. overnight. A 5% (w/w) aqueous
suspension of the material then was prepared, and stirred for about 30
minutes with gentle heating in order to ensure complete dispersion. The
results are summarized in Table 1, and are as follows: ANC, 0.925;
Appearance, translucent; Stability, excellent; Grittiness, none;
Evaluation, preferred.
EXAMPLE 8
DASC(Room Temp); 70% Sorbitol After Filtration
147 g (1.75 moles) of sodium bicarbonate were added to 540 g of water at
room temperature. 306 g (1.5 moles) of aluminum iso-propoxide then were
added to the mixture and stirred. The resulting precipitate was isolated
by vacuum filtration, and then reslurried with 128 g of a 70% sorbitol
solution (i.e. 90 g of 100% sorbitol and 38 g of water). After mixing, the
resulting mixture was air dried, and then oven dried at 100.degree. C.
overnight. A 5% (w/w) aqueous suspension of the material then was
prepared, and stirred for about 30 minutes with gentle heating in order to
ensure complete dispersion. The results are summarized in Table 1, and are
as follows: ANC, 0.910; Appearance, translucent; Stability, excellent;
Grittiness, none; Evaluation, preferred.
EXAMPLE 9
DASC(Hot); 70% Sorbitol After Filtration
147 g (1.75 moles) of sodium bicarbonate were added to 540 g of water, and
heated to 60-70.degree. C. 306 g (1.5 moles) of aluminum iso-propoxide
then were added to the mixture and stirred for 1 hour. The resulting
precipitate was isolated by vacuum filtration, and then reslurried with
128 g of a 70% sorbitol solution (i.e. 90 g of 100% sorbitol and 38 g of
water). After mixing, the resulting mixture was air dried, and then oven
dried at 100.degree. C. overnight. A 5% (w/w) aqueous suspension of the
material then was prepared, and stirred for about 30 minutes with gentle
heating in order to ensure complete dispersion. The results are summarized
in Table 1, and are as follows: ANC, not determined; Appearance,
translucent; Stability, excellent; Grittiness, none; Evaluation,
acceptable.
EXAMPLE 10
DASC(Hot); 50% Sorbitol After Filtration
147 g (1.75 moles) of sodium bicarbonate were added to 540 g of water. 306
g (1.5 moles) of aluminum iso-propoxide, heated to about 100.degree. C.,
then were added to the mixture and stirred for 1 hour. The resulting
precipitate was isolated by vacuum filtration, and then reslurried with
180 g of a 50% sorbitol solution (i.e. 90 g of 100% sorbitol and 90 g of
water). After mixing for 1 hour, the resulting mixture was air dried, and
then oven dried at 100.degree. C. overnight. A 5% (w/w) aqueous suspension
of the material then was prepared, and stirred for about 30 minutes with
gentle heating in order to ensure complete dispersion. The results are
summarized in Table 1, and are as follows: ANC, 0.905; Appearance,
translucent; Stability, excellent; Grittiness, none; Evaluation,
preferred.
EXAMPLE 11
DASC(Hot); 30% Sorbitol After filtration
147 g (1.75 moles) of sodium bicarbonate were added to 540 g of water. 306
g (1.5 moles) of aluminum iso-propoxide, heated to 100.degree. C., then
were added to the mixture and stirred for 1 hour. The resulting
precipitate was isolated by vacuum filtration, and then reslurried with
300 g of a 30% sorbitol solution (i.e. 90 g of 100% sorbitol and 210 g of
water). After mixing for 1 hour, the resulting mixture was air dried, and
then oven dried at 100.degree. C. overnight. A 5% (w/w) aqueous suspension
of the material then was prepared, and stirred for about 30 minutes with
gentle heating in order to ensure complete dispersion. The results are
summarized in Table 1, and are as follows: ANC, 0.990; Appearance,
translucent; Stability, excellent; Grittiness, none; Evaluation,
preferred.
EXAMPLE 12
DASC(Hot): 10% Sorbitol After Filtration
147 g (1.75 moles) of sodium bicarbonate were added to 540 g of water. 306
g (1.5 moles) of aluminum iso-propoxide, heated to 100.degree. C., then
were added to the mixture and stirred for 1 hour. The resulting
precipitate was isolated by vacuum filtration, and then reslurried with 51
g of a 70% sorbitol solution (i.e. 36 g of 100% sorbitol and 15 g of
water). After mixing for 1 hour, the resulting mixture was air dried, and
then oven dried at 100.degree. C. overnight. A 5% (w/w) aqueous suspension
of the material then was prepared, and stirred for about 30 minutes with
gentle heating in order to ensure complete dispersion. The results are
summarized in Table 1, and are as follows: ANC, 1.159; Appearance,
translucent; Stability, excellent; Grittiness, none; Evaluation,
preferred.
EXAMPLE 13
DASC(Hot); 5% Sorbitol After Filtration
147 g (1.75 moles) of sodium bicarbonate were added to 540 g of water. 306
g (1.5 moles) of aluminum iso-propoxide, heated to 100.degree. C., then
were added to the mixture and stirred for 1 hour. The resulting
precipitate was isolated by vacuum filtration, and then reslurried with 26
g of a 70% sorbitol solution (i.e. 18 g of 100% sorbitol and 8 g of
water). After mixing for 1 hour, the resulting mixture was air dried, and
then oven dried at 100.degree. C. overnight. A 5% (w/w) aqueous suspension
of the material then was prepared, and stirred for about 30 minutes with
gentle heating in order to ensure complete dispersion. The results are
summarized in Table 1, and are as follows: ANC, 1.109; Appearance,
semi-translucent; Stability, excellent; Grittiness, minor; Evaluation,
acceptable.
EXAMPLE 14
DASC(Hot); Glycerin After Filtration
147 g (1.75 moles) of sodium bicarbonate were added to 540 g of water. 306
g (1.5 moles) of aluminum iso-propoxide, heated to 100.degree. C., then
were added to the mixture and stirred for 1 hour. The resulting
precipitate was isolated by vacuum filtration, and then reslurried with 90
g of glycerin and enough water to form a homogeneous slurry. After mixing
for 1 hour, the resulting mixture was air dried, and then oven dried at
100.degree. C. overnight. A 5% (w/w) aqueous suspension of the material
then was prepared, and stirred for about 30 minutes with gentle heating in
order to ensure complete dispersion. The results are summarized in Table
1, and are as follows: ANC, 0.926; Appearance, semi-translucent;
Stability, excellent; Grittiness, none; Evaluation, acceptable.
EXAMPLE 15
DASC(Room Temp.); 50% Glycerin After Filtration
295.6 g (3.53 moles) of sodium bicarbonate were added to 2400 g of water.
629 g (3.1 moles) of aluminum iso-propoxide then were added to the mixture
and stirred for 1 hour at room temperature. The resulting precipitate was
isolated by vacuum filtration. 50% of the filter cake then was added to a
mixture of 46 g of glycerin dissolved in 700 g of water. After stirring
for 10 minutes, the resulting mixture was fan dried, and then oven dried
at 105-110.degree. C. overnight. A 5% (w/w) aqueous suspension of the
material then was prepared, and stirred for about 30 minutes with gentle
heating in order to ensure complete dispersion. The results are summarized
in Table 1, and are as follows: ANC, 1.158; Appearance, opaque; Stability,
excellent; Grittiness, none; Evaluation, unacceptable for liquid antacids
(acceptable for gelled antacids).
EXAMPLE 16
DASC(Hot); Mannitol After Filtration
147 g (1.75 moles) of sodium bicarbonate were added to 540 g of water. 306
g (1.5 moles) of aluminum iso-propoxide, heated to 100.degree. C., then
were added to the mixture and stirred for 1 hour. The resulting
precipitate was isolated by vacuum filtration, and then reslurried with 90
g of mannitol dissolved in 495 g of water. After mixing for 1 hour, the
resulting mixture was air dried, and then oven dried at 100.degree. C.
overnight. A 5% (w/w) aqueous suspension of the material then was
prepared, and stirred for about 30 minutes with gently heating in order to
ensure complete dispersion. The results are summarized in Table 1, and are
as follows: ANC, 1.150; Appearance, translucent; Stability, excellent;
Grittiness, none; Evaluation, preferred.
EXAMPLE 17
DASC(Room Temp.): 50% Mannitol After Filtration
287.6 g (3.42 moles) of sodium bicarbonate were added to 2400 g of water.
612 g (3.0 moles) of aluminum iso-propoxide then were added to the mixture
and stirred for 1 hour at room temperature. The resulting precipitate was
isolated by vacuum filtration. 50% of the filter cake was then added to a
mixture of 44.8 g of mannitol dissolved in 1000 g of water. After stirring
for 10 minutes, the resulting mixture was fan dried, and then oven dried
at 105-110.degree. C. overnight. A 5% (w/w) aqueous suspension of the
material then was prepared, and stirred for about 30 minutes with gentle
heating in order to ensure complete dispersion. The results are summarized
in Table 1, and are as follows: ANC, 1.067; Appearance, semi-translucent;
Stability, excellent; Grittiness, minor; Evaluation, unacceptable for
liquid antacids (acceptable for gelled antacids).
EXAMPLE 18
DASC(Room Temp.); Inositol After Filtration
287.6 g (3.42 moles) of sodium bicarbonate were added to 2400 g of water.
612 g (3.0 moles) of aluminum iso-propoxide then were added to the mixture
and stirred for 1 hour at room temperature. The resulting precipitate was
isolated by vacuum filtration. 50% of the filter cake was then added to a
mixture of 89.6 g of inositol dissolved in 900 g of water. After stirring
for 10 minutes, the resulting mixture was fan dried, and then oven dried
at 105.degree.-110.degree. C. overnight. A 5% (w/w) aqueous suspension of
the material then was prepared, and stirred for about 30 minutes with
gentle heating in order to ensure complete dispersion. The results are
summarized in Table 1, and are as follows: ANC, 0.809; Appearance,
semi-opaque; Stability, some settling; Grittiness, bad; Evaluation,
unacceptable.
EXAMPLE 19
DASC(Room Temp.); 50% Inositol After Filtration
287.6 g (3.42 moles) of sodium bicarbonate were added to 2400 g of water.
612 g (3.0 moles) of aluminum iso-propoxide then were added to the mixture
and stirred for 1 hour at room temperature. The resulting precipitate was
isolated by vacuum filtration. 50% of the filter cake was then added to a
mixture of 44.8 g of inositol dissolved in 700 g of water. After stirring
for 10 minutes, the resulting mixture was fan dried, and then oven dried
at 105.degree.-110.degree. C. overnight. A 5% (w/w) aqueous suspension of
the material then was prepared, and stirred for about 30 minutes with
gentle heating in order to ensure complete dispersion. The results are
summarized in Table 1, and are as follows: ANC, 1.025; Appearance, opaque;
Stability, separated; Grittiness, none; Evaluation, unacceptable.
EXAMPLE 20
DASC(Hot); Pentaerythritol After Filtration
147 g (1.75 moles) of sodium bicarbonate were added to 540 g of water. 306
g (1.5 moles) of aluminum iso-propoxide, heated to 100.degree. C., then
were added to the mixture and stirred for 1 hour. The resulting
precipitate was isolated by vacuum filtration, and then reslurried with 90
g of pentaerythritol dissolved in 270 g of warm water. After mixing for 1
hour, the resulting mixture was air dried, and then oven dried at
100.degree. C. overnight. A 5% (w/w) aqueous suspension of the material
then was prepared, and stirred for about 30 minutes with gentle heating in
order to ensure complete dispersion. The results are summarized in Table
1, and are as follows: ANC, 0.885; Appearance, translucent; Stability,
excellent; Grittiness, none; Evaluation, preferred.
EXAMPLE 21
DASC(Room Temp.); 50% Pentaerythritol After Filtration
287.6 g (3.42 moles) of sodium bicarbonate were added to 2400 g of water.
615 g (3.0 moles) of aluminum iso-propoxide then were added to the mixture
and stirred for 1 hour at room temperature. The resulting precipitate was
isolated by vacuum filtration. 50% of the filter cake was then added to a
mixture of 44.8 g of pentaerythritol dissolved in 700 g of water. After
stirring for 10 minutes, the resulting mixture was fan dried, and then
oven dried at 105.degree.110.degree. C. overnight. A 5% (w/w) aqueous
suspension of the material then was prepared, and stirred for about 30
minutes with gentle heating in order to ensure complete dispersion. The
results are summarized in Table 1, and are as follows: ANC, 1.077;
Appearance, translucent; Stability, separated; Grittiness, none;
Evaluation, unacceptable.
EXAMPLE 22
DASC(Hot); Sucrose After Filtration
147 g (1.75 moles) of sodium bicarbonate were added to 540 g of water. 306
g (1.5 moles) of aluminum iso-propoxide, heated to 100.degree. C., then
were added to the mixture and stirred for 1 hour. The resulting
precipitate was isolated by vacuum filtration, and then reslurried with 90
g of sucrose dissolved in 38 g of water. After mixing for 1 hour, the
resulting mixture was air dried, and then oven dried at 100.degree. C.
overnight. A 5% (w/w) aqueous suspension of the material then was
prepared, and stirred for about 30 minutes with gentle heating in order to
ensure complete dispersion. The results are summarized in Table 1, and are
as follows: ANC, 0.945; Appearance, semi-opaque; Stability, bad settling;
Grittiness, bad; Evaluation, unacceptable.
EXAMPLE 23
DASC(Hot); Maltodextrin After Filtration
147 g (1.75 moles) of sodium bicarbonate were added to 540 g of water. 306
g (1.5 moles) of aluminum iso-propoxide, heated to 100.degree. C., then
were added to the mixture and stirred for 1 hour. The resulting
precipitate was isolated by vacuum filtration, and then reslurried with 90
g of maltodextrin dissolved in 38 g of water. After mixing for 1 hour, the
resulting mixture was air dried, and then oven dried at 100.degree. C.
overnight. A 5% (w/w) aqueous suspension of the material then was
prepared, and stirred for about 30 minutes with gentle heating in order to
ensure complete dispersion. The results are summarized in Table 1, and are
as follows: ANC, 0.885; Appearance, translucent; Stability, excellent;
Grittiness, none; Evaluation, preferred.
EXAMPLE 24
DASC(Room Temp.); Acacia After Filtration
287.6 g (3.42 moles) of sodium bicarbonate were added to 2400 g of water.
612 g (3.0 moles) of aluminum iso-propoxide then were added to the mixture
and stirred for 1 hour at room temperature. The resulting precipitate was
isolated by vacuum filtration. 50% of the filter cake was then added to a
mixture of 89.6 g of acacia dissolved in 900 g of water. After stirring
for 10 minutes, the resulting mixture was fan dried, and then oven dried
at 105-110.degree. C. overnight. A 5% (w/w) aqueous suspension of the
material then was prepared, and stirred for about 30 minutes with gentle
heating in order to ensure complete dispersion. The results are summarized
in Table 1, and are as follows: ANC, 0.853; Appearance, opaque; Stability,
bad settling; Grittiness, bad; Evaluation, unacceptable.
EXAMPLE 25
DASC(Room Temp.); Fructose After Filtration
287.6 g (3.42 moles) of sodium bicarbonate were added to 2400 g of water.
617 g (3.0 moles) of aluminum iso-propoxide then were added to the mixture
and stirred for 1 hour at room temperature. The resulting precipitate was
isolated by vacuum filtration. 50% of the filter cake was then added to a
mixture of 89.6 g of fructose dissolved in 700 g of water. After stirring
for 10 minutes, the resulting mixture was fan dried, and then oven dried
at 105-110.degree. C. overnight. A 5% (w/w) aqueous suspension of the
material then was prepared, and stirred for about 30 minutes with gentle
heating in order to ensure complete dispersion. The results are summarized
in Table 1, and are as follows: ANC, 0.920; Appearance, translucent;
Stability, excellent; Grittiness, none; Evaluation, preferred.
EXAMPLE 26
DASC(Hot); Propylene Glycol After Filtration
147 g (1.75 moles) of sodium bicarbonate were added to 540 g of water. 306
g (1.5 moles) of aluminum iso-propoxide, heated to 100.degree. C., then
were added to the mixture and stirred for 1 hour. The resulting
precipitate was isolated by vacuum filtration, and then reslurried with 90
g of propylene glycol and enough water to form a homogeneous slurry. After
mixing for 1 hour, the resulting mixture was air dried, and then oven
dried at 100.degree. C. overnight. A 5% (w/w) aqueous suspension of the
material then was prepared, and stirred for about 30 minutes with gentle
heating in order to ensure complete dispersion. The results are summarized
in Table 1, and are as follows: ANC, 0.970; Appearance, semi-opaque;
Stability, minor settling; Grittiness, bad; Evaluation, unacceptable.
EXAMPLE 27
DASC(Hot); 1,3-Butylene Glycol After Filtration
147 g (1.75 moles) of sodium bicarbonate were added to 540 g of water. 306
g (1.5 moles) of aluminum iso-propoxide, heated to 100.degree. C., then
were added to the mixture and stirred for 1 hour. The resulting
precipitate was isolated by vacuum filtration, and then reslurried with 90
g of 1,3-butylene glycol and enough water to form a homogeneous slurry.
After mixing for 1 hour, the resulting mixture was air dried, and then
oven dried at 100.degree. C. overnight. A 5% (w/w) aqueous suspension of
the material then was prepared, and stirred for about 30 minutes with
gentle heating in order to ensure complete dispersion. The results are
summarized in Table 1, and are as follows: ANC, 0.992; Appearance, opaque;
Stability, bad settling; Grittiness, bad; Evaluation, unacceptable.
EXAMPLE 28
DASC(Hot); Neopentyl Glycol After Filtration
147 g (1.75 moles) of sodium bicarbonate were added to 540 g of water. 306
g (1.5 moles) of aluminum iso-propoxide, heated to 100.degree. C., then
were added to the mixture and stirred for 1 hour. The resulting
precipitate was isolated by vacuum filtration, and then reslurried with 90
g of neopentyl glycol dissolved in 38 g of water. After mixing for 1 hour,
the resulting mixture was air dried, and then oven dried at 100.degree. C.
overnight. A 5% (w/w) aqueous suspension of the material then was
prepared, and stirred for about 30 minutes with gentle heating in order to
ensure complete dispersion. The results are summarized in Table 1, and are
as follows: ANC, 1.005; Appearance, opaque; Stability, bad settling;
Grittiness, bad; Evaluation, unacceptable.
EXAMPLE 29
DASC(Room Temp.); PEG (200 MW) After Filtration
287.6 g (3.42 moles) of sodium bicarbonate were added to 2400 g of water.
612 g (3.0 moles) of aluminum iso-propoxide then were added to the mixture
and stirred for 1 hour at room temperature. The resulting precipitate was
isolated by vacuum filtration. 50% of the filter cake then was added to a
mixture of 89.6 g of polyethylene glycol (200 MW) dissolved in 700 g of
water. After stirring for 10 minutes, the resulting mixture was fan dried,
and then oven dried at 105-110.degree. C. overnight. A 5% (w/w) aqueous
suspension of the material then was prepared, and stirred for about 30
minutes with gentle heating in order to ensure complete dispersion. The
results are summarized in Table 1, and are as follows: ANC, 0.820;
Appearance, opaque; Stability, separated; Grittiness, bad; Evaluation,
unacceptable.
EXAMPLE 30
DASC(Room Temp.); PEG (1500 MW) After Filtration
287.6 g (3.42 moles) of sodium bicarbonate were added to 2400 g of water.
612 g (3.0 moles) of aluminum iso-propoxide then were added to the mixture
and stirred for 1 hour at room temperature. The resulting precipitate was
isolated by vacuum filtration. 50% of the filter cake was then added to a
mixture of 89.6 g of polyethylene glycol (1500 MW) dissolved in 700 g of
water. After stirring for 10 minutes, the resulting mixture was fan dried,
and then oven dried at 105-110.degree. C. overnight. A 5% (w/w) aqueous
suspension of the material then was prepared, and stirred for about 30
minutes with gentle heating in order to ensure complete dispersion. The
results are summarized in Table 1, and are as follows: ANC, 0.869;
Appearance, opaque; Stability, bad settling; Grittiness, bad; Evaluation,
unacceptable.
EXAMPLE 31
DASC(Hot); Sodium Carboxymethylcellulose After Filtration
49 g (0.58 moles) of sodium bicarbonate were added to 180 g of water. 102 g
(0.50 moles) of aluminum iso-propoxide, heated to 100.degree. C., then
were added to the mixture and stirred for 1 hour. The resulting
precipitate was isolated by vacuum filtration, and then reslurried with 30
g of sodium carboxymethylcellulose dispersed in 200 g of water. After
mixing for 1 hour, the resulting mixture was air dried, and then oven
dried at 100.degree. C. overnight. A 5% (w/w) aqueous suspension of the
material then was prepared, and stirred for about 30 minutes with gentle
heating in order to ensure complete dispersion. The results are summarized
in Table 1, and are as follows: ANC, not determined; Appearance, opaque;
Stability, solidified; Grittiness, bad; Evaluation, unacceptable.
EXAMPLE 32
Replace AIP With ASB; Sorbitol After Filtration
143.7 g (1.7 moles) of sodium bicarbonate were added to 2000 g of water.
364.6 g (1.5 moles) of aluminum sec-butoxide then were added to the
mixture and stirred for 1 hour at room temperature. The resulting
precipitate was isolated by vacuum filtration. 50% of the filter cake was
then added to 64 g of a 70% sorbitol solution (i.e. 45 g of 100% sorbitol
and 19 g of water) dissolved in 350 g of water. After stirring for 10
minutes, the resulting mixture was fan dried, and then oven dried at
105.degree.110.degree. C. overnight. A 5% (w/w) aqueous suspension of the
material then was prepared, and stirred for about 30 minutes with gentle
heating in order to ensure complete dispersion. The results are summarized
in Table 1, and are as follows: ANC, 0.964; Appearance, translucent;
Stability, excellent; Grittiness, minor; Evaluation, acceptable.
TABLE 1
______________________________________
Ex. ANC Appearance Stability
Grit. Evaluation*
______________________________________
1 N.D. opaque bad settl.
bad unacceptable
2 1.265 semi-opaque excellent
none acceptable
3 1.065 semi-opaque excellent
none acceptable
4 0.920 opaque bad settl.
bad unacceptable
5 0.947 translucent excellent
none preferred
6 0.677 translucent excellent
none acceptable
7 0.925 translucent excellent
none preferred
8 0.910 translucent excellent
none preferred
9 N.D. translucent excellent
none acceptable
10 0.905 translucent excellent
none preferred
11 0.990 translucent excellent
none preferred
12 1.159 translucent excellent
none preferred
13 1.109 translucent excellent
minor acceptable
14 0.926 semi-trans. excellent
none acceptable
15 1.158 opaque excellent
none unacceptable
16 1.150 translucent excellent
none preferred
17 1.067 semi-trans. excellent
minor unacceptable
18 0.809 semi-opaque some settl.
bad unacceptable
19 1.025 opaque separated
none unacceptable
20 0.885 translucent excellent
none preferred
21 1.077 translucent separated
none unacceptable
22 0.945 semi-opaque bad settl.
bad unacceptable
23 0.885 translucent excellent
none preferred
24 0.853 opaque bad settl.
bad unacceptable
25 0.920 translucent excellent
none preferred
26 0.970 semi-opaque minor settl.
bad unacceptable
27 0.992 opaque bad settl.
bad unacceptable
28 1.005 opaque bad settl.
bad unacceptable
29 0.820 opaque separated
bad unacceptable
30 0.869 opaque bad settl.
bad unacceptable
31 N.D. opaque solidified
bad unacceptable
32 0.964 translucent excellent
minor acceptable
______________________________________
*Evaluation based upon preferred suspensions for use in liquid antacid
formulations. The preferred criteria were met by those suspensions having
an ANC>0.8 (mEq of acid consumed per gram of suspension tested, as
determined using Method 301 of USP23), translucent appearance, excellent
stability and no grittiness. Examples 15 and 17, although unacceptable for
liquid antacids, are acceptable for gelled antacids.
All issued U.S. patents mentioned hereinabove are hereby incorporated by
reference in their entirety.
While the foregoing invention has been described in some detail for
purposes of clarity and understanding, it will be appreciated by one
skilled in the art from a reading of the disclosure that various changes
in form and detail can be made without departing from the true scope of
the invention in the appended claims.
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